TGF-β signaling is required for multiple processes during Xenopus tail regeneration
TGF-β signaling is required for multiple processes during Xenopus tail regeneration
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DOI：
10.1016/j.ydbio.2007.12.031
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发表时间：
2008-03-01
影响因子：
2.7
通讯作者：
Whitman, Malcolm
中科院分区：
文献类型：
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作者：
Ho, Diana M.;Whitman, Malcolm
非洲爪哇蝌蚪可以在尾巴截断后完全再生所有主要组织类型。在整个发育和成年期，转化生长因子-β信号在组织的生长、修复、规范和分化中起着至关重要的作用。我们研究了再生过程中转化生长因子-β信号通路的关键成分的定位，并表征了转化生长因子-β信号的缺失对多种再生事件的影响。磷酸化的Smad2(p-Smad2)最初局限于再生上皮的p63+基底层，后来在再生芽中的多种组织类型中发现。转化生长因子-β配体在整个再生过程中也被上调。SB-431542是转化生长因子-β信号转导的特异性和可逆性抑制剂，可在多个点阻止尾巴再生。在尾巴截断后立即抑制转化生长因子-β信号可逆地防止在未来的再生芽上形成伤口上皮。然而，即使在截肢后立即进行短暂的抑制，也足以不可逆转地阻止表征再生组织的结构和细胞类型的建立，并阻止BMP和ERK信号通路的适当激活。再生后对转化生长因子-β信号的抑制已经开始阻止再生芽中的细胞增殖。这些数据揭示了在再生过程中转化生长因子-β信号在空间和时间上的几个不同的作用：(1)伤口上皮的形成，(2)再生芽结构和信号级联的建立，以及(3)细胞增殖的调节。(C)2007 Elsevier Inc.保留所有权利。
Xenopus tadpoles can fully regenerate all major tissue types following tail amputation. TGF-beta signaling plays essential roles in growth, repair, specification, and differentiation of tissues throughout development and adulthood. We examined the localization of key components of the TGF-beta signaling pathway during regeneration and characterized the effects of loss of TGF-beta signaling on multiple regenerative events. Phosphorylated Smad2 (p-Smad2) is initially restricted to the p63+ basal layer of the regenerative epithelium shortly after amputation, and is later found in multiple tissue types in the regeneration bud. TGF-beta ligands are also upregulated throughout regeneration. Treatment of amputated tails with SB-431542, a specific and reversible inhibitor of TGF-beta signaling, blocks tail regeneration at multiple points. Inhibition of TGF-beta signaling immediately following tail amputation reversibly prevents formation of a wound epithelium over the future regeneration bud. Even brief inhibition immediately following amputation is sufficient, however, to irreversibly block the establishment of structures and cell types that characterize regenerating tissue and to prevent the proper activation of BMP and ERK signaling pathways. Inhibition of TGF-beta signaling after regeneration has already commenced blocks cell proliferation in the regeneration bud. These data reveal several spatially and temporally distinct roles for TGF-beta signaling during regeneration: (1) wound epithelium formation, (2) establishment of regeneration bud structures and signaling cascades, and (3) regulation of cell proliferation. (C) 2007 Elsevier Inc. All rights reserved.